From the Guidelines
GLP-1 agonists primarily cause fat loss rather than muscle loss, with approximately 70-80% of the weight lost coming from fat tissue, particularly visceral fat around the organs, which is metabolically beneficial. These medications, including semaglutide and liraglutide, work by mimicking the hormone GLP-1, which regulates appetite and food intake by acting on the brain's hunger centers 1. When people take these medications, they typically experience reduced hunger, increased feelings of fullness, and slower gastric emptying, which leads to decreased caloric intake.
Some key points to consider when using GLP-1 agonists for weight loss include:
- The STEP trials, which examined the efficacy of semaglutide, found that mean weight loss at 68 weeks was 14.9% and 16.0% in the STEP 1 and STEP 3 trials, respectively, with a significant difference from placebo 1.
- A meta-analysis of GLP-1 receptor agonists reported that subcutaneous semaglutide reduced weight and improved weight-related comorbidities significantly more than liraglutide and was associated with lower rates of gastrointestinal adverse events 1.
- To minimize any potential muscle loss while taking these medications, patients are advised to maintain adequate protein intake (1.2-2.0 g/kg of body weight daily) and engage in regular resistance training at least 2-3 times per week, which helps preserve lean muscle mass while the medications primarily target fat stores.
The benefits of GLP-1 agonists on cardiovascular health are also notable, with a meta-analysis showing that these medications decrease the risk of CVD events in adults with overweight or obesity without diabetes 1. Additionally, the SELECT study found that semaglutide reduced the composite incidence of death due to cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke at 39.8 months 1.
Overall, the evidence suggests that GLP-1 agonists are a effective treatment for obesity, primarily causing fat loss rather than muscle loss, and also providing benefits for cardiovascular health.
From the Research
GLP-1 Agonists and Weight Loss
- GLP-1 agonists, such as liraglutide and semaglutide, have been shown to reduce body weight and improve glucose metabolism in patients with type 2 diabetes 2, 3, 4, 5, 6.
- A systematic review and meta-analysis found that semaglutide had a greater mean weight loss compared to liraglutide and dulaglutide, but tirzepatide had a greater mean weight loss compared to semaglutide 6.
Effects on Muscle and Fat Loss
- A study found that liraglutide and semaglutide protected skeletal muscle against obesity-induced muscle atrophy via the SIRT1 pathway, suggesting that GLP-1 agonists may help preserve muscle mass while promoting fat loss 3.
- Another study found that GLP-1 receptor agonists, including semaglutide, liraglutide, and dulaglutide, demonstrated mean weight loss reductions, with semaglutide showing increased numerical weight loss compared to its comparators 6.
Comparison of GLP-1 Agonists
- A review of head-to-head clinical studies found that all GLP-1 receptor agonists are effective therapeutic options for reducing A1C, but differences exist in terms of magnitude of effect on A1C and weight, as well as frequency of adverse effects 5.
- A systematic review and meta-analysis found that semaglutide, liraglutide, dulaglutide, tirzepatide, and exenatide demonstrated mean weight loss reductions, with tirzepatide producing greater weight loss compared to semaglutide 6.